Somatic mutation of PTEN in bladder carcinoma

The tumour suppressor gene PTEN/MMAC1, which is mutated or homozygously del eted in glioma, breast and prostate cancer, is mapped to a region of 10q wh ich shows loss of heterozygosity (LOH) in bladder cancer. We screened 123 b ladder tumours for LOH in the region of PTEN. In 53 informative muscle inva sive tumours (greater than or equal to pT2), allele loss was detected in 13 (24.5%) and allelic imbalance in four tumours (overall frequency 32%). LOH was found in four of 60 (6.6%) informative, non-invasive tumours (pTa/pT1) . We screened 63 muscle invasive tumours for PTEN mutations by single-stran d conformation polymorphism (SSCP) analysis and for homozygous deletion by duplex quantitative polymerase chain reaction (PCR). Two homozygous deletio ns were identified but no mutations. Of 15 bladder tumour cell lines analys ed, three showed homozygous deletion of all or part of the PTEN gene, but n one had mutations detectable by SSCP analysis. Our results indicate that PT EN is involved in the development of some bladder tumours. The low frequenc y of mutation of the retained allele in tumours with 10q23 LOH suggests tha t there may be another predominant mechanism of inactivation of the second allele, for example small intragenic deletions, that hemizygosity may be su fficient for phenotypic effect, or that there is another target gene at 10q 23.